Effects of grape seed proanthocyanidins extracts on AGEs and expression of bone morphogenetic protein-7 in diabetic rats.
BACKGROUND
Diabetic nephropathy (DN) is the most common cause of end-stage renal failure. Grape seed proanthocyanidin extracts (GSPEs) are powerful antioxidants. However, the role of GSPEs in advanced glycation end products (AGEs), expression of connective tissue growth factor (CTGF) and bone morphogenetic protein-7 (BMP-7) in DN has not been elucidated. Using streptozotocin-induced diabetic rats, we evaluated the effects of GSPE in DN.


METHODS
Wistar rats were induced into diabetes using streptozotocin injections, and diabetic rats were treated with GSPE (high dosage: 500 mg/kg per day; low dosage: 250 mg/kg.per day) for 24 weeks. The renal pathologic changes were examined with periodic acid-Schiff (PAS) staining under an electron microscope. The mRNA and protein expressions of CTGF and BMP-7 in kidney were detected by RT-PCR and immunohistochemical staining.


RESULTS
Treated animals showed a reduction in serum AGEs (p<0.01), proteinuria (p<0.01) and systolic blood pressure (SBP) (p<0.01). GSPE reduced the expression of mRNA and protein of CTGF in the kidney (p<0.05 and p<0.01), which were contributing to reversal of extracellular matrix (ECM) accumulation in DN. GSPE increased the expression of mRNA and protein of BMP-7 in the kidney (p<0.05 and p<0.01), which were contributing to improvement of the microstructure of podocytes and ECM accumulation in DN.


CONCLUSIONS
Our results suggest that GSPEs hold substantial promise for the treatment of DN. GSPEs can decrease proteinuria and attenuate the progression of nephropathy in diabetic rats. Renoprotective effects of GSPE correlated with suppression of AGEs, down-regulating expression of CTGF and up-regulating the expression of BMP-7.
Li
Xianhua
X
Department of Nephrology, Qi Lu Hospital of Shangdong University, Jinan - PR China.
Xu
Ling
L
Gao
Haiqing
H
Li
Baoying
B
Cheng
Mei
M
D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism*; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000517:prevention & control; D005109:Extracellular Matrix / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000097:blood*; D056604:Grape Seed Extract; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D055419:Bone Morphogenetic Protein 7; C526316:CCN2 protein, rat; D017127:Glycation End Products, Advanced; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D010936:Plant Extracts; D044945:Proanthocyanidins; D055513:Connective Tissue Growth Factor